SLC22A3
protein-codingsolute carrier family 22 member 3, the group of Solute carrier family 22
Gene summary
Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~104.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SLC22A3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021977.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 71 | 1 | 72 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 74 | 2 | 0 | 76 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_068812.1 | 11 | MANE Select | |
| Ensembl | ENSP00000275300.2 | 11 | MANE Select | |
| Ensembl | ENSP00000525271.1 | 7 | Standard | |
| Ensembl | ENSP00000525271.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Choline metabolism in cancer - Homo sapiens (human)
- Lamivudine Pathway, Pharmacokinetics/Pharmacodynamics
- Metformin Pathway, Pharmacokinetics
- Sympathetic Nerve Pathway (Neuroeffector Junction)
- Lamivudine Metabolism Pathway
Biological Process
- drug transmembrane transport
- organic cation transport
- quaternary ammonium group transport
- regulation of appetite
- histamine uptake
Molecular Function
- dopamine:sodium symporter activity
- protein binding
- organic cation transmembrane transporter activity
- quaternary ammonium group transmembrane transporter activity
- toxin transmembrane transporter activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000275300
- Coding exons
- 11
- Length
- 106715
- Individuals with no LoFs
- 125692
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 51
- Defined
- 125743
- p
- 0.000203
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.485 | 279 | 303 | 0.922 | 0.0000166 | 3516 |
| Missense (PolyPhen) | 123 | 133.24 | 0.92317 | 1558 | ||
| Synonymous | -0.359 | 126 | 121 | 1.04 | 0.00000675 | 1172 |
| Loss of Function | 1.42 | 18 | 25.8 | 0.697 | 0.00000130 | 286 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00055 | 0.00054 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00012 | 0.00012 | rare |
| South Asian | 0.00052 | 0.00052 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain. {ECO:0000269|PubMed:10196521, ECO:0000269|PubMed:10966924}.;
Recessive Scores
- pRec
- 0.173
Intolerance Scores
- LoFtool
- 0.682
- RVIS EVS
- -0.45
- RVIS percentile EVS
- 24.19
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.181
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |